[Experimental obstruction of the retinal and choroid vessels in monkeys]. Klöti R Bibliotheca ophthalmologica : supplementa ad ophthalmologica
    Experimental retinal detachment in owl monkeys. Effect of intravitreal hyaluronidase injection and embolization of the choroidal and retinal circulation. Algvere P,Balazs E A Modern problems in ophthalmology
    The mesothelium: a cytochemical study of "activated" mesothelial cells. Whitaker D,Papadimitriou J M,Walters M N The Journal of pathology The cytochemical profile of activated mesothelial cells differs from resting cells. The reaction products of enzymes associated with oxidative mechanisms of cell respiration were easily displayed in activated mesothelial cells; in resting mesothelial cells, only enzymes of the pentose pathway were readily demonstrable. Acid hydrolases were detected in greater quantity than in resting cells, possibly reflecting an increased potential for endocytosis. In addition, the cytochemical assays indicated increased Golgi activity was reflected by the demonstration of thiamine pyrophosphatase, while the content of ribonucleic acid was also increased. These cytochemical features compare well with the ultrastructure of active mesothelial cells which possess abundant ergastoplasm and a well-developed Golgi apparatus. In comparison with peritoneal macrophages, activated mesothelial cells differ mainly in the quantity of reaction product, there being more in macrophages. The results were significantly different only in the demonstration of lipids which were never found in mesothelial cells, but were invariably present in macrophages. It is still unclear whether the acid mucopolysaccharide hyaluronic acid is produced by or merely transported through the mesothelium from the subserosal site. 10.1002/path.1711360302
    Blindness following cosmetic injections of the face. Lazzeri Davide,Agostini Tommaso,Figus Michele,Nardi Marco,Pantaloni Marcello,Lazzeri Stefano Plastic and reconstructive surgery BACKGROUND:Complications following facial cosmetic injections have recently heightened awareness of the possibility of iatrogenic blindness. The authors conducted a systematic review of the available literature to provide the best evidence for the prevention and treatment of this serious eye injury. METHODS:The authors included in the study only the cases in which blindness was a direct consequence of a cosmetic injection procedure of the face. RESULTS:Twenty-nine articles describing 32 patients were identified. In 15 patients, blindness occurred after injections of adipose tissue; in the other 17, it followed injections of various materials, including corticosteroids, paraffin, silicone oil, bovine collagen, polymethylmethacrylate, hyaluronic acid, and calcium hydroxyapatite. CONCLUSIONS:Some precautions may minimize the risk of embolization of filler into the ophthalmic artery following facial cosmetic injections. Intravascular placement of the needle or cannula should be demonstrated by aspiration before injection and should be further prevented by application of local vasoconstrictor. Needles, syringes, and cannulas of small size should be preferred to larger ones and be replaced with blunt flexible needles and microcannulas when possible. Low-pressure injections with the release of the least amount of substance possible should be considered safer than bolus injections. The total volume of filler injected during the entire treatment session should be limited, and injections into pretraumatized tissues should be avoided. Actually, no safe, feasible, and reliable treatment exists for iatrogenic retinal embolism. Nonetheless, therapy should theoretically be directed to lowering intraocular pressure to dislodge the embolus into more peripheral vessels of the retinal circulation, increasing retinal perfusion and oxygen delivery to hypoxic tissues. CLINICAL QUESTION/LEVEL OF EVIDENCE:Risk, V. 10.1097/PRS.0b013e3182442363
    A new vascular sealant (Sealgel) to achieve rapid hemostasis after percutaneous angioplasty in anticoagulated patients: clinical feasibility and preliminary results. Lefebvre J M,Qanadli S D,Kacher S,Aberkane L,Rigaud M,Lacombe P,Rocha P European radiology The aim of this study was to assess the feasibility of a new vascular sealant (Sealgel) to provide rapid hemostasis in anticoagulated patients after percutaneous transluminal angioplasty (PTA). Sealgel was designed with ancrod (10 mg) and tranexamic acid (80 mg) dissolved in a hyaluronic acid gel (3 ml). Fifty anticoagulated patients (heparin, aspirin, ticlopidin) who underwent PTA of coronary artery were enrolled in the study. Sealgel (3 ml) was delivered under manual compression through a 9-F cannula at the arterial puncture site after the introducer sheath removal at the end of PTA procedure. Hemostasis time as well as complications were recorded. Sealgel was successfully delivered in 98 % of patients. Hemostasis occurred within 15 mn of manual compression in 82 % of patients, within 25 mn in 98 %, and failed in 1 patient (2 %). Hematoma (6-cm diameter) was observed in 1 patient and late bleeding in another one. There were no clinical signs of embolism, inflammatory swelling, local infection, vascular fistula, or pseudoaneurysm. No surgery or blood transfusion was required. Sealgel application after PTA in anticoagulated patient is feasible and secure. Preliminary results suggest that the Sealgel brought about rapid hemostasis; however further studies are needed to determine its clinical efficacy. 10.1007/s003300000642
    The infraorbital artery: Clinical relevance in esthetic medicine and identification of danger zones of the midface. Hufschmidt K,Bronsard N,Foissac R,Baqué P,Balaguer T,Chignon-Sicard B,Santini J,Camuzard O Journal of plastic, reconstructive & aesthetic surgery : JPRAS BACKGROUND:Over the past decade, cosmetic injections of dermal fillers or fat have become a popular procedure in facial rejuvenation in an overconsuming society. However, complications such as arterial embolism and occlusion can occur even with experienced injectors, especially in high-risks zones namely the glabella, the nasal dorsum or the nasolabial fold. The aim of this study was to define the vascular danger zones of the infraorbital area in order to provide guidelines helping avoid them. MATERIALS AND METHODS:The infraorbital artery, its main branches and their anastomoses with neighbouring vessels were studied in 18 fresh cadavers. Mimetic injections of inked hyaluronic acid were performed in the infraorbital area in the interest of analyzing its distribution and to determine potential vascular risks towards the infraorbital artery and its branches. RESULTS:The infraorbital artery and its branches were located in common injection regions and anastomosed to the supratrochlear artery, the dorsal nasal artery and the angular artery through the nasal branch of the infraorbital artery. Two danger zones could be depicted: injections can be risky when performed too superficially in the midcheek area, and likewise risky when performed in a periosteal layer in infraorbital hollow or tear-trough correction, because of an obvious possibility of retrograde embolism. CONCLUSION:The infraorbital artery can be involved in anatomic mechanism of arterial occlusion, further blindness and stroke, among the related neighbouring arteries. Based on the findings of this study, injections to the periosteum layer in tear-trough correction and above the periosteum on the zygomatic arch is not advised. 10.1016/j.bjps.2018.09.010
    Pathophysiology Study of Filler-Induced Blindness. Cho Ki-Hyun,Dalla Pozza Edoardo,Toth Gabor,Bassiri Gharb Bahar,Zins James E Aesthetic surgery journal Background:A number of authors have proposed retrograde arterial embolism as the responsible mechanism for filler-induced blindness. However, no previous human study has substantiated this proposed mechanism. Objectives:The aim of this study was to investigate the pathophysiology of filler-induced blindness using a fresh cadaver perfusion technique. Methods:A fresh cadaver head perfusion model that simulates both physiologic blood pressure and flow rate of the carotid artery, ophthalmic artery, and supratrochlear artery was used. The common carotid artery was cannulated and the internal jugular vein exposed for open venous drainage. A plasma-based perfusate was circulated through the cadaver head, which was connected to a perfusion system consisting of a roller pump, preload reservoir, and pressure monitor. The hyaluronic acid filler mixed with methylene blue was injected into the cannulated superficial branch of the supratrochlear artery. Cadaver dissection, angiographic study, and histology were used to investigate filler-induced blindness. Results:Cannulation of the superficial branch of the supratrochlear artery was successful in all six cadavers. Emboli to the ophthalmic artery was successfully demonstrated in the three out of 6 fresh cadaver heads. The C-arm angiogram documented a cut-off sign in the ophthalmic artery due to hyaluronic acid filler emboli. An average intravascular volume of the intraorbital part of the supratrochlear artery was 50.0 µL. The average depth of location of the superficial branch of the supratrochlear artery from the epidermal surface was 1.5 mm. Conclusions:Our cadaveric study demonstrated that retrograde hyaluronic acid filler emboli to the ophthalmic artery could be produced by the cannulation of the supratrochlear artery. The superficial location of the supratrochlear artery, the rich vasculature surrounding it, and the variability in the anatomy make this possible. 10.1093/asj/sjy141
    Pulmonary embolism after intra-articular injection of methylprednisolone and hyaluronate. Famularo G,Liberati C,Sebastiani G D,Polchi S Clinical and experimental rheumatology
    External and Internal Diameters of the Facial Artery Relevant to Intravascular Filler Injection. Lee Shin-Hyo,Ha Tae-Jun,Koh Ki-Seok,Song Wu-Chul Plastic and reconstructive surgery BACKGROUND:Vision loss and skin necrosis caused by an accidental intraarterial embolism or vascular compression are rare but devastating complications when injecting filler materials into the face. METHODS:The external and internal diameters and wall thicknesses of the facial artery and its branches were measured from 41 formalin-embalmed cadavers after removing connective tissues attached to the arterial wall. RESULTS:The diameter and thickness of the facial artery exhibited significant interregional differences. The external and internal diameters of the facial artery were 1.9 ± 0.4 and 1.2 ± 0.3 mm (mean ± SD), respectively, at the inferior border of the mandible; 1.7 ± 0.3 and 1.2 ± 0.3 mm in the vicinity of the inferior labial artery; 1.5 ± 0.3 and 1.0 ± 0.3 mm at the mouth corner; 1.4 ± 0.3 and 0.9 ± 0.2 mm in the vicinity of the superior labial artery; and 1.1 ± 0.2 and 0.7 ± 0.2 mm in the vicinity of the lateral nasal artery. The external and internal diameters at the proximal parts of the inferior labial artery, superior labial artery, and lateral nasal artery were 1.0 ± 0.3 and 0.6 ± 0.2 mm, 0.9 ± 0.3 and 0.6 ± 0.2 mm, and 0.8 ± 0.2 and 0.5 ± 0.2 mm, respectively. CONCLUSION:Morphometric examinations of the facial artery under stereomicroscope observation as performed in the present study are expected to be more accurate than direct measurements obtained during cadaveric dissection or conventional histologic evaluations. 10.1097/PRS.0000000000005428
    Pulmonary emboli from therapeutic sodium hyaluronate. Bhagat Rajesh,Forteza Rosanna M,Calcote Clay B,Williams William T,Bigler Steven A,Dwyer Terry M Respiratory care A patient presented with shortness of breath and pleuritic pain shortly after bilateral knee synovial injections with sodium hyaluronate (HA). He was discharged after a brief hospitalization without a diagnosis when no Doppler or radiologic evidence of deep vein thrombosis or pulmonary emboli was found. Radiologic studies found patchy ground glass opacities that were predominantly peripheral in disposition, with prominent septal lines in the lungs; a subsequent pulmonary function test showed a reduced diffusing capacity of the lung for carbon monoxide (D(LCO)). These results prompted a lung biopsy that revealed multiple emboli composed of HA and fibrin in medium size pulmonary arteries, enlarged lymphatic vessels, and a bone marrow embolus. This is the first report of HA emboli following therapeutic HA injections and demonstrates that pulmonary function tests can be used to infer the reduction in pulmonary vascular area consequent to pulmonary emboli, and so can contribute to the detection of pulmonary emboli in unusual presentations. 10.4187/respcare.01666
    Demarcative Necrosis Along Previous Laceration Line After Filler Injection. Kim Jong-Lim,Shin Jin Yong,Roh Si-Gyun,Lee Nae-Ho The Journal of craniofacial surgery In recent years, fillers have been widely used for soft tissue augmentation. Although they are generally considered to be safe, many complications have been reported to date. Nose and nasolabial fold augmentations with fillers can lead to an implementation of nasal skin necrosis, possibly caused by intravascular embolism and/or extravascular compression. Herein, we present a case of a successfully treated patient who experienced skin necrosis after an injection of dermal fillers into the nasolabial fold. Interestingly, we discovered that the patient had experienced a laceration 8 years ago around the area in which the filler was injected. 10.1097/SCS.0000000000003791
    Elevated hyaluronan levels in patients with rheumatic mitral stenosis and pulmonary arterial thromboembolism. Kalay Nihat,Elcik Deniz,Savaş Göktuğ,Altın Pınar,Şakalar Çağrı,Kaya Öznur,Aytekin Metin Heart, lung & circulation INTRODUCTION:The role of hyaluronan (HA) was previously demonstrated in patients with idiopathic pulmonary arterial hypertension (PAH). Mitral stenosis (MS) and pulmonary arterial thromboembolism (PTE) are important health problems that can cause pulmonovascular pathology. Pulmonary arterial hypertension develops especially in untreated patients with severe MS and most of patients with PTE. However, there is no data about HA levels in patients with MS and PTE. In this study, we investigated HA levels in patients with rheumatic MS and PTE. METHOD:Study population was divided into three groups. MS group consisted of 18 patients with moderate or severe MS. PTE group consisted of 16 patients with PTE. Control group consisted of 15 subjects without cardiac and pulmonary disease. Percutaneous mitral balloon valvuloplasty (PMV) was performed on all patients in MS group. Mitral gradients and systolic pulmonary arterial pressure (sPAP) were measured in all patients. HA levels were measured at baseline and first month after PMV. RESULTS:Mean sPAP±SD (mmHg) was 23±3 in the control group, 44±9 in the MS group and 66±11 in the PTE group (p<0.001). Baseline serum HA levels were significantly correlated with sPAP(echo) (r=0.332 p=0.03) and sPAP(cath) (r=0.559, p=0.007). Serum HA levels (ng/ml) in MS were significantly higher compared to controls [39±14 vs 24±11; p=0.01]. Patients in PTE group had the highest HA levels (61±21; p<0.001). Serum HA levels were significantly decreased at the first month after PMV in patients with MS [MS group: 39±14 (ng/ml), after PMV: 31±8; p=0.03]. CONCLUSION:This is the first article showing that both MS and PTE can cause increased serum HA levels. HA levels were decreased with PMV procedure in patients with MS. 10.1016/j.hlc.2014.01.011
    Arterial embolization and skin necrosis of the nasal ala following injection of dermal fillers. Inoue Keita,Sato Katsujiro,Matsumoto Daisuke,Gonda Koichi,Yoshimura Kotaro Plastic and reconstructive surgery 10.1097/01.prs.0000300188.82515.7f
    Do you know where your fillers go? An ultrastructural investigation of the lips. Vent Julia,Lefarth Florian,Massing Thomas,Angerstein Wolfgang Clinical, cosmetic and investigational dermatology AIM:To investigate the exact location and position of hyaluronic acid fillers in the perioral region by ultrasound and optical coherence tomography. INTRODUCTION:To date, there are few in vivo investigations in humans on the exact positioning of injectable hyaluronic acid fillers, and severe complications such as hematoma and thromboembolism are rarely addressed. MATERIALS AND METHODS:There were nine female patients investigated in this pilot study. All of them were periorally injected with hyaluronic acid. The exact product, amount, and locations, as well as the injection techniques, were recorded and compared. Before, immediately after, and 18 days after injection, photo documentation as well as high-resolution ultrasonography and optical coherence tomography of the lip surface were performed. RESULTS:Minor bruising occurred, which resolved within 7 to 9 days. On day 18, no more hemorrhage could be detected. Injected material distributed well in the tissue, and no embolism or thrombosis occurred. However, the injected material came close (up to 1 mm) to important structures such as blood vessels. Lip wrinkles improved, and the lip surface was smoother and more even. CONCLUSION:Hyaluronic acid injections can improve aesthetics and reduce fine wrinkles of the lips. In the patients investigated in this study, compression of structures such as vessels and nerve fibers did not occur, nor did any severe complications result from injection. However, one must be aware of serious complications (eg, hematoma, thromboembolism) and the important anatomic structures (eg, orbicularis oris muscle, vessels, and nerves), and injecting physicians should always have hyaluronidase as a rescue medication at hand. SUMMARY:Hyaluronic acid is a suitable tool for lip augmentation and reduction of fine lines; however, one must be aware of anatomic structures when injecting filler material into the lips and perioral area, and be familiar with the injection techniques. 10.2147/CCID.S63093
    Adverse reactions to injectable soft tissue fillers: memorable cases and their clinico-pathological overview. Lee Soo-Keun,Kim So Min,Cho Sang Hyun,Lee Jeong Deuk,Kim Hei Sung Journal of cosmetic and laser therapy : official publication of the European Society for Laser Dermatology BACKGROUND:Filler injection is a minimally invasive procedure widely used for soft tissue augmentation. Although the safety profile is favorable, adverse events can occur, especially after illegal filler injection. OBJECTIVES:The authors present memorable cases of filler complications and review their clinico-pathological features and treatment strategies. PATIENTS AND METHODS:This is a retrospective, single-center case series. The authors identified eight patients with significant complications following filler injection. A medical record review was performed for clinical history, histopathological studies, and treatment. RESULTS:Six female and two male subjects presented with significant filler complications. The time interval between filler injection and the development of a complication varied greatly among cases (immediately afterwards to 14 years following filler injection). Four of the patients received illegal filler injection where the injected material was either unknown (25%) or was told as paraffin (12.5%) or Vaseline(®) (12.5%). Hyaluronic acid fillers were used in two patients (25%) and the rest were injected with porcine atelocollagen (12.5%) and polyacrylamide hydrogel (12.5%). The complications were classified as an allergic reaction (25%), filler material migration (12.5%), injection necrosis + embolism (25%), and foreign body granuloma (37.5%), based on their clinico-pathological features and were treated accordingly. CONCLUSION:Adverse effects are not uncommon following filler injection. Physicians should be aware of the potential side effects, recognize their presentations, and understand how to manage them. 10.3109/14764172.2014.968584
    Imaging of nonthrombotic pulmonary embolism: biological materials, nonbiological materials, and foreign bodies. Bach Andreas Gunter,Restrepo Carlos Santiago,Abbas Jasmin,Villanueva Alberto,Lorenzo Dus María José,Schöpf Reinhard,Imanaka Hideaki,Lehmkuhl Lukas,Tsang Flora Hau Fung,Saad Fathinul Fikri Ahmad,Lau Eddie,Rubio Alvarez Jose,Battal Bilal,Behrmann Curd,Spielmann Rolf Peter,Surov Alexey European journal of radiology Nonthrombotic pulmonary embolism is defined as embolization to the pulmonary circulation caused by a wide range of substances of endogenous and exogenous biological and nonbiological origin and foreign bodies. It is an underestimated cause of acute and chronic embolism. Symptoms cover the entire spectrum from asymptomatic patients to sudden death. In addition to obstruction of the pulmonary vasculature there may be an inflammatory cascade that deteriorates vascular, pulmonary and cardiac function. In most cases the patient history and radiological imaging reveals the true nature of the patient's condition. The purpose of this article is to give the reader a survey on pathophysiology, typical clinical and radiological findings in different forms of nonthrombotic pulmonary embolism. The spectrum of forms presented here includes pulmonary embolism with biological materials (amniotic fluid, trophoblast material, endogenous tissue like bone and brain, fat, Echinococcus granulosus, septic emboli and tumor cells); nonbiological materials (cement, gas, iodinated oil, glue, metallic mercury, radiotracer, silicone, talc, cotton, and hyaluronic acid); and foreign bodies (lost intravascular objects, bullets, catheter fragments, intraoperative material, radioactive seeds, and ventriculoperitoneal shunts). 10.1016/j.ejrad.2012.09.019
    Gluteal Augmentation Techniques: A Comprehensive Literature Review. Oranges Carlo M,Tremp Mathias,di Summa Pietro G,Haug Martin,Kalbermatten Daniel F,Harder Yves,Schaefer Dirk J Aesthetic surgery journal Background:Many studies of gluteal augmentation techniques have been published in recent decades, including case reports, retrospective and prospective case series, and multicenter survey reviews. However, to date, there has been no study of the overall complications or satisfaction rates associated with the broad spectrum of techniques. Objectives:The authors performed a comprehensive literature review to determine outcomes and complications of gluteoplasty techniques, including patient satisfaction. Methods:A search on PubMed/Medline was performed for clinical studies involving gluteal augmentation techniques. A priori criteria were used to review the resulting articles. Results:Fifty-two studies, published from 1969 through 2015, were included - representing 7834 treated patients. Five gluteal augmentation techniques were identified from these studies: gluteal augmentation with implants (n = 4781), autologous fat grafting (n = 2609), local flaps (n = 369), hyaluronic acid gel injection (n = 69), and local tissue rearrangement (n = 6). The overall complication rates of the most commonly utilized techniques were: 30.5% for gluteal augmentation with implants, 10.5% for autologous fat grafting, and 22% for local flaps. Patients' satisfaction was reported as consistently high for all the five techniques. Conclusions:Implant-based gluteal augmentation is associated with high patients' satisfaction despite a high complication rate, while autologous fat grafting is associated with the lowest complication rate yet including serious major complications such as fat embolism. Local flaps and local tissue rearrangements are the ideal procedures in case of massive weight loss patients. A paucity of data is available for hyaluronic acid gel injections, which appear to be effective but temporary and expensive. Level of Evidence 4: 10.1093/asj/sjw240
    Anatomic Study of Ophthalmic Artery Embolism Following Cosmetic Injection. Wu Sufan,Pan Lei,Wu Hua,Shi Hangyan,Zhao Ye,Ji Yu,Zeng Haifeng The Journal of craniofacial surgery INTRODUCTION:Cosmetic injections of dermal fillers or fat could cause ophthalmic artery embolism and even blindness, the high-risk regions of which are considered glabellar, nasal dorsum, and nasolabial fold. Understanding anatomy of the related arteries is important for a physician to safely perform filler injections. To investigate the mechanisms of ophthalmic artery embolism following the injections, cadaver anatomy was studied. METHODS:Ophthalmic artery, facial artery, their branches, and anastomoses among them were anatomized in 12 fresh cadavers. Mimetic injections of hyaluronic acid were performed in glabellar region, nasal dorsum, and nasolabial fold, the relationships between injected filler and related arteries were then investigated. RESULTS:It was clearly found that 4 arteries were located in common injection regions and connected to ophthalmic artery: supratrochlear artery, supraorbital artery, dorsal nasal artery, and angular artery. In the glabellar region, the deep injection on the periosteum will be risky to injure supratrochlear artery and supraorbital artery, whereas in nasal dorsum and nasolabial fold, the sub- superficial musculo aponeurotic system layer injection has the possibility to injure dorsal nasal artery, angular artery, and facial artery. CONCLUSION:The anatomic mechanism of ophthalmic artery embolism is the anastomoses among the related arteries and ophthalmic artery. Based on the findings of the study, injections in periosteum layer at glabellar region or sub-superficial musculo aponeurotic system layer of nasal dorsum and nasolabial fold are not advised. 10.1097/SCS.0000000000003674
    Blindness caused by cosmetic filler injection: a review of cause and therapy. Carruthers Jean D A,Fagien Steve,Rohrich Rod J,Weinkle Susan,Carruthers Alastair Plastic and reconstructive surgery Vascular occlusion causing blindness is a rare yet greatly feared complication of the use of facial aesthetic fillers. The authors performed a review of the aesthetic literature to ascertain the reported cases of blindness and the literature reporting variations in the vascular anatomy of the human face. The authors suggest a small but potentially helpful addition to the accepted management of the acute case. Cases of blindness, mostly irreversible, from aesthetic filler injections have been reported from Asia, Europe, and North America. Autologous fat appears to be the most frequent filler causing blindness. Some cases of partial visual recovery have been reported with hyaluronic acid and calcium hydroxylapatite fillers. The sudden profusion of new medical and nonmedical aesthetic filler injectors raises a new cause for alarm about patient safety. The published reports in the medical literature are made by experienced aesthetic surgeons and thus the actual incidence may be even higher. Also, newer injectors may not be aware of the variations in the pattern of facial vascular arborization. The authors present a summary of the relevant literature to date and a suggested helpful addition to the protocols for urgent management. 10.1097/PRS.0000000000000754
    Arterial embolization caused by injection of hyaluronic acid (Restylane). Schanz S,Schippert W,Ulmer A,Rassner G,Fierlbeck G The British journal of dermatology 10.1046/j.1365-2133.2002.04707.x
    Arterial embolization caused by injection of hyaluronic acid (Restylane). Lowe N J The British journal of dermatology 10.1046/j.1365-2133.2003.05097_13.x
    Ultrasonography-guided Cannula Method for Hyaluronic Acid Filler Injection with Evaluation using Laser Speckle Flowgraphy. Iwayama Takanori,Hashikawa Kazunobu,Osaki Takeo,Yamashiro Kenjiro,Horita Nobuyuki,Fukumoto Takeshi Plastic and reconstructive surgery. Global open Hyaluronic acid (HA) is present in the connective tissues of the skin and decreases with age. HA fillers are popular as facial rejuvenation treatments. They are generally considered safe; however, complications, such as cutaneous necrosis and blindness due to vascular embolism, sometimes occur. Because vascular embolisms are likely associated with the deep placement of HA fillers, a strategy that involves injection into superficial regions (the conventional method) is commonly used to reduce risks. However, deep injections to achieve revolumization are becoming common, even in high-risk areas for intravascular infusion. We aimed to study the usefulness of the ultrasonography-guided cannula method for preventing intravascular infusion of HA fillers. An HA filler was injected into the region just under the dermis on the left side of the face of a 38-year-old man using the conventional method, and another HA filler was injected into the periosteum on the right side using the ultrasonography-guided cannula method. The skin blood flow on both sides was compared using laser speckle flowgraphy (LSFG). The ultrasonography-guided method was successful in detecting the cannula and the blood vessel, and the HA filler was safely injected into a deep region. Using LSFG, a difference in skin blood flow between the 2 methods was detected. The ultrasonography-guided cannula method was effective in aiding the safe injection of an HA filler in a deep high-risk area and maintained skin blood flow. LSFG may be adopted to evaluate skin blood flow after HA filler injections. 10.1097/GOX.0000000000001776
    Retinal branch artery occlusion following injection of hyaluronic acid (Restylane). Peter Silvia,Mennel Stefan Clinical & experimental ophthalmology The authors report a retinal branch artery occlusion occurring after facial injection of a dermal filler. The superior temporal artery showed occlusion due to a clearly visible long and fragmented embolus suggestive of gel and clearly distinguishable from calcific or cholesterol emboli. The authors suppose that hyaluronic acid gel was embolized in the patient. The embolized material is supposed to enter the ocular circulation through retrograde arteriolar flow after intra-arterial injection into one of the peripheral branches of the ophthalmic artery. If there is any evidence of a visual problem after facial injection of a dermal filler, prompt consultation of an ophthalmologist is recommended. 10.1111/j.1442-9071.2006.01224.x
    [What's new in interventional dermatology?] Raimbault C Annales de dermatologie et de venereologie This year, many publications have focused on understanding, avoiding and treating vascular complications when injecting fillers. New protocols for the use of hyaluronidase have shown their effectiveness in preventing skin necrosis or blindness after vascular embolism when injecting hyaluronic acid. Other areas of interventional dermatology have been well documented: myomodulation is an interesting concept that describes the impact of the injection depth of a filler on muscle forces in order to correct the balances between the lowering and elevators during congenital or acquired defcits with aging. Treatment of melasma remains diffcult but the prescription of oral tranexamic acid could be useful. Botulinum toxin is expanding its feld of activity for both aesthetic and medical treatments. Pulsed dye laser remains the reference treatment for port wine stains, but the rate of recurrence by post laser neo-angiogenesis justifes the need of reliable and effective adjuvant treatments. 10.1016/S0151-9638(18)31284-5
    The Risk of Skin Necrosis Following Hyaluronic Acid Filler Injection in Patients with a History of Cosmetic Rhinoplasty. Robati Reza M,Moeineddin Fatemeh,Almasi-Nasrabadi Mina Aesthetic surgery journal Background:As the number of patients using dermal filler for face augmentation increases, the number of adverse events associated with injection may increase. Unpredictable repositioning of blood vessels and a more tenuous blood supply in the operated nose may increase the risk of ischemia, necrosis and vascular embolism following the filler injection. Objectives:To highlight the importance of the patient's history of previous cosmetic procedures including rhinoplasty in the emergence of vascular complications. Methods:Our medical records over a two-year period were reviewed retrospectively to identify all patients who were treated at our center for vascular complications associated with facial hyaluronic acid filler injections. In each case, the subject's demographic data (gender and age), habitual status, past medical and surgical history, the symptoms and clinical presentation at the first visit, the time interval between the injection and the onset of symptoms, injected filler material and brand, injection sites, the introduced treatment, and photographs were reviewed carefully. Results:A total of seven patients were identified, each developing skin necrosis following injection of the hyaluronic acid filler. All patients reported a cosmetic rhinoplasty more than three years ago. Conclusions:Our finding confirms the conjecture previously made in the literature and suggests that the distinctive vascularity of the nose and the surrounding area may cause filler augmentation induced vascular complications in patients whose vascular circulation has already been compromised by a previous nose surgery. 10.1093/asjour/sjy005
    A Rethink on Hyaluronidase Injection, Intraarterial Injection, and Blindness: Is There Another Option for Treatment of Retinal Artery Embolism Caused by Intraarterial Injection of Hyaluronic Acid? Goodman Greg J,Clague Mike D Dermatologic surgery : official publication for American Society for Dermatologic Surgery [et al.] 10.1097/DSS.0000000000000670
    Severe vision loss caused by cosmetic filler augmentation: Case series with review of cause and therapy. Thanasarnaksorn Wilai,Cotofana Sebastian,Rudolph Christina,Kraisak Patcharahatai,Chanasumon Nongsak,Suwanchinda Atchima Journal of cosmetic dermatology Hyaluronic acid (HA) injection is a popular nonsurgical, facial rejuvenating procedure. Due to the rapidly expanding use of HA injections, significant potential complications have also increased in frequency. Among these complications, the rare but most devastating one is arterial occlusion, which can result in skin necrosis or blindness. To describe the mechanisms behind vision loss secondary to hyaluronic acid injection and the efficacy of treatments to restore vision and associated ocular functionality. We reviewed six cases of patients from October 2011 to December 2017 who experienced vision loss after receiving facial HA injections and the subsequent treatments undertaken to attempt to reverse the vision loss and additional eye complications. Of the six patients, four received nose, one received forehead, and another one received temple injections. All six patients developed vision loss secondary to hyaluronic acid embolization in retinal or ophthalmic arteries. Additional complications included severe periorbital pain, ptosis, impairment of extraocular muscle functionality. Recovery of vision was dependent on the type, frequency, and duration of subsequent treatment. Vision loss is a rare but catastrophic complication caused by hyaluronic injection that occurs secondary to hyaluronic acid embolization in retinal or ophthalmic arteries due to retrograde flow from facial vascular anastomoses. We suggest the early supratrochlear/supraorbital hyaluronidase injection, ocular massage, and re-breathing into a plastic bag as safe, uncomplicated and effective methods to restore the retinal circulation and reverse vision loss. 10.1111/jocd.12705
    Clinical Observations and the Anatomical Basis of Blindness After Facial Hyaluronic Acid Injection. Zhang Lei,Pan Lei,Xu Hong,Yan Sheng,Sun Yi,Wu Woffles T L,Wu Sufan Aesthetic plastic surgery BACKGROUND:Blindness or visual loss is the most serious complication resulting from facial hyaluronic acid (HA) injection. In this study, three recent clinical cases were analyzed, and the relevant anatomy of cadavers was evaluated to investigate the mechanism behind visual impairment due to HA injection. METHODS:Three patients with different extents of visual loss after HA injection were studied. Ophthalmic testing and corresponding treatments were performed, and the clinical progress was observed. In addition, thirty-six fresh Asian cadaver hemifaces were anatomized to investigate the morphology of the ophthalmic artery and its branches. The minimum dose of HA for central retinal artery embolism was calculated based on the ophthalmic arterial volumes of cadavers. RESULTS:Visual impairment was more severe in central retinal artery occlusion and combined intraocular branch occlusion than in posterior ciliary artery occlusion. During follow-up, no improvement was observed in terms of visual impairment. Cadaver study reconfirmed that the ophthalmic artery included facial and intraocular branches. The ophthalmic arterial volumes running from the supraorbital artery and supratrochlear artery to the central retinal artery were 0.083 cm and 0.089 cm, respectively. CONCLUSIONS:The severity of blindness caused by HA injection may be associated with the occlusion site. Our clinical observations indicate that conventional treatments, such as retrobulbar hyaluronidase injection, are insufficient to relieve visual impairment. Injecting as little as 0.08 ml of HA into the facial branch is enough to cause central retinal artery embolism. Limiting the volume per injection could represent a simple prophylactic strategy. LEVEL OF EVIDENCE V:This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 . 10.1007/s00266-019-01374-w
    Experimentally Induced Arterial Embolism by Hyaluronic Acid Injection: Clinicopathological Observations and Treatment. Chen Yin,Zhang You-Liang,Luo Sheng-Kang Plastic and reconstructive surgery BACKGROUND:Although major complications of hyaluronic acid (HA) injection rarely occur, with the rapidly growing number of procedures performed and their expanding applications, such complications warrant greater attention. Our study was designed to explore optimal treatment methods for HA-related vascular occlusion. METHODS:Part I: Thirty rats were given intra-arterial HA injected into the bilateral inferior epigastric arteries to establish an animal model and were euthanized at different post-injection time points. The inferior epigastric artery was retrieved for pathological examination. Part II: Bilateral abdominal flaps supplied by the inferior epigastric artery were elevated in six groups of rats, and HA was injected into the right side, with each group receiving a different intervention. The flap-survival rate was calculated and analyzed. RESULTS:Part I: Pathological examination revealed that the composition of the emboli caused by arterial HA-induced occlusion changed from pure HA to an HA-thrombus mixture.Part II: Flap-survival rates (mean percentages):Group A: 43.29±9.28%, Group B: 54.17±10.86%,Group C: 59.27±13.40%, Group D: 64.37±8.61%,Group E: 71.92±19.06%, Group F: 57.47±13.64%Group A differed significantly from groups B, C, D, and E (p<0.001). No significant difference was observed between groups A and F (p>0.05). CONCLUSION:The combined use of intravenous or subcutaneous hyaluronidase and urokinase was most effective in treating HA injection-related arterial embolism after 45 min and 24 h. This treatment may be ineffective after 48 h. 10.1097/PRS.0000000000005456
    Blindness After Facial Filler Injections: The Role of Extravascular Hyaluronidase on Intravascular Hyaluronic Acid Embolism in the Rabbit Experimental Model. Zhang Lei,Feng Xiao,Shi Hangyan,Wu Woffles T L,Wu Sufan Aesthetic surgery journal BACKGROUND:Blindness caused by ophthalmic artery embolism is the most catastrophic complication of facial hyaluronic acid (HA) injections. Extravascular (retrobulbar) injection of hyaluronidase has been suggested as a salvage in this calamitous situation. However, the effectiveness of this treatment still lacks consensus. OBJECTIVES:The aim of this study was to investigate the role of extravascular hyaluronidase in dissolving intravascular HA occlusion. METHODS:Two different animal experiments were performed: (1) isolated rabbit abdominal aorta segments filled with HA were treated with extravascular immersion of highly concentrated hyaluronidase for 90 minutes, followed by gross observation, microscopic examination, particle size analysis, and immunohistochemical staining; and (2) live rabbit auricular arteries were first occluded with HA and then immediately treated with extravascular injection of hyaluronidase. The ears were then evaluated by gross observation, microscopic examination, and perfusion studies after 60 minutes and again after 90 minutes. RESULTS:The HA within the aorta segments showed no gross or microscopic changes after treatment with extravascular hyaluronidase. Hyaluronidase could only be detected in adventitia of the aortae, instead of in vascular smooth muscle, tunica intima, or vascular lumen. The occluded auricular arteries showed no reperfusion after extravascular injection of hyaluronidase. CONCLUSIONS:In this rabbit model, extravascular hyaluronidase was unable to penetrate into the arterial lumen of the isolated abdominal aorta or the live auricular artery of the rabbit to dissolve intravascular HA within a 90-minute time limit, thus casting doubt on whether extravascular (retrobulbar) hyaluronidase injection has a role in treating ophthalmic artery embolism caused by HA injections. 10.1093/asj/sjz280
    An In Vitro Model Assessing the Penetration of Hyaluronidase through Optic Nerve Dura for Management of Hyaluronic Acid Facial Filler Embolism. Adulkar Namrata,Cheng Charles,Lee Lawrence,Rasmussen Steve,Dolman Peter J,Yin Vivian T Plastic and reconstructive surgery BACKGROUND:Blindness from ophthalmic or central retinal artery embolism is one of the most devastating complications of cosmetic filler facial injections. A proposed therapy to mitigate visual loss is prompt retrobulbar injection of hyaluronidase into the retrobulbar space. Despite Zhu et al. showing a lack of evidence and very limited published literature for reversing visual loss with this intervention, it is still widely accepted as a treatment for filler-related emboli. The purpose of this study was to evaluate the penetration of hyaluronidase through optic nerve dura using an in vitro model. METHODS:At study conclusion, five 1-cm-long segments of fresh optic nerve were obtained and injected with highly crosslinked hyaluronic acid filler, then ligated on both ends in a watertight fashion. The sections were immersed in three concentrations of hyaluronidase solution for 24 hours. Histopathologic examination of the specimen was performed to assess the presence of filler. RESULTS:The optic nerve sections were 1.1 cm (range, 0.8 to 1.2 cm). Three were immersed in 20 ml of 1500 IU/ml hyaluronidase solution and two were immersed in saline as control. After 24 hours, there was a persistence of hyaluronic acid within the optic nerves. CONCLUSIONS:There is a lack of evidence for penetration of optic nerve sheath by hyaluronidase. This raises question about the effectiveness of retrobulbar injection of hyaluronidase in reversing filler-related blindness. Further studies are needed before this can be adopted as the treatment of choice. CLINICAL QUESTION/LEVEL OF EVIDENCE:Therapeutic, V. 10.1097/PRS.0000000000005714
    Treatment of skin soft tissue embolism after hyaluronic acid injection for injection rhinoplasty in Asian patients. Ouyang Hua-Wei,Li Gao-Feng,Zhu Yi,Lei Ying,Gold Michael H,Tan Jun Journal of cosmetic dermatology INTRODUCTION:The purpose of this manuscript is to investigate the treatment of skin soft tissue embolization or vascular occlusion after the injection of hyaluronic acid (HA) for Injection Rhinoplasty (IR) in Asians with a special interest in the time occurrence of the occlusion. METHODS:A total of 35 cases were evaluated after receiving HA injections for IR who presented with a vascular occlusive event. They were divided into three stages based on the time to embolization. Immediate, ≤5 hours; early, ≤3 days; and late, >3 days. There were two cases of immediate, 28 deemed early, and five late. Methods to prevent tissue necrosis are reviewed in the manuscript based on these stages. RESULTS:Skin color gradually recovered to normal after 11 treatments in 11 patients with mild embolization. No ischemic aggravation or skin necrosis was observed in 19 patients with moderate embolization; red scarring was seen in two and hypertrophic scar with uneven skin color in one patient. The five patients in the severe category had longer healing, more red scars, and more hypertrophic scarring. CONCLUSION:The treatment of skin soft tissue embolization or vascular occlusion after HA IR in Asians can be effected by identifying the stage and degree of embolization and treating appropriately with the outlines presented in this manuscript. 10.1111/jocd.12968
    A Histopathologic Diagnosis of Vascular Occlusion After Injection of Hyaluronic Acid Filler: Findings of Intravascular Foreign Body and Skin Necrosis. Maruyama Seiichi Aesthetic surgery journal Before injecting hyaluronic acid (HA) filler into high-risk zones of the face, considerable caution must be exercised, including careful selection of the most appropriate filler, volume, and injection technique. Rare but severe adverse events have occurred during and after injection of HA filler in or around the periorbital region, such as skin necrosis and blindness. In the present case, involving a 57-year-old woman, approximately 0.1 mL of HA was injected into each side of the glabella to minimize wrinkles. The filler was injected into the dermis, utilizing the linear threading method. Proper care and caution were exercised before and during the procedure. Two days later, purple discoloration and erythema were observed in the left glabellar zone and forehead. A biopsy specimen was obtained and, based on histopathologic examination, frontal skin necrosis secondary to vascular occlusion was diagnosed. The likely cause and mechanism of the embolism will be discussed. To the author's knowledge, histopathologic findings of an intravascular remnant after injection of HA appear to be rare. LEVEL OF EVIDENCE:5. 10.1093/asj/sjx085
    Clinical Application of Earlobe Augmentation with Hyaluronic Acid Filler in the Chinese Population. Qian Wei,Zhang Yan-Kun,Cao Qian,Hou Ying,Lv Wei,Fan Ju-Feng Aesthetic plastic surgery BACKGROUND:Larger earlobes, which are a symbol of "richness" in traditional Chinese culture, are favored by Chinese patients. The objective of this paper is to investigate the application of earlobe augmentation with hyaluronic acid (HA) filler injection and its clinical effects in the Chinese population. METHODS:A total of 19 patients (38 ears) who received earlobe augmentation with HA filler injections between March 2013 and March 2015 were included. The clinical effects, duration, and complications of these cases were investigated. RESULTS:All patients who received earlobe HA injections showed immediate postoperative effects with obvious morphological improvement of their earlobes. The volume of HA filler injected into each ear was 0.3-0.5 ml. The duration of the effect was 6-9 months. Two of the 19 cases (3 ears) demonstrated mild bruising at the injection site, but the bruising completely disappeared within 7 days after the injection. No vascular embolism, infection, nodule, or granuloma complications were observed in the studied group. CONCLUSION:The application of earlobe augmentation with HA filler injection is a safe, effective, simple procedure for earlobe shaping. It has an easy clinical application with good clinical prospects. LEVEL OF EVIDENCE V:This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 . 10.1007/s00266-016-0742-6
    Clinical Outcomes of Impending Nasal Skin Necrosis Related to Nose and Nasolabial Fold Augmentation with Hyaluronic Acid Fillers. Sun Zhong-Sheng,Zhu Guo-Zhang,Wang Hai-Bin,Xu Xiang,Cai Bing,Zeng Li,Yang Jin-Qing,Luo Sheng-Kang Plastic and reconstructive surgery BACKGROUND:Although there are several case reports of facial skin ischemia/necrosis caused by hyaluronic acid filler injections, no systematic study of the clinical outcomes of a series of cases with this complication has been reported. METHODS:The authors report a study of 20 consecutive patients who developed impending nasal skin necrosis as a primary concern, after nose and/or nasolabial fold augmentation with hyaluronic acid fillers. The authors retrospectively reviewed the clinical outcomes and the risk factors for this complication using case-control analysis. RESULTS:Seven patients (35 percent) developed full skin necrosis, and 13 patients (65 percent) recovered fully after combination treatment with hyaluronidase. Although the two groups had similar age, sex, filler injection sites, and treatment for the complication, 85 percent of the patients in the full skin necrosis group were late presenters who did not receive the combination treatment with hyaluronidase within 2 days after the vascular complication first appeared. In contrast, just 15 percent of the patients in the full recovery group were late presenters (p = 0.004). CONCLUSIONS:Nose and nasolabial fold augmentations with hyaluronic acid fillers can lead to impending nasal skin necrosis, possibly caused by intravascular embolism and/or extravascular compression. The key for preventing the skin ischemia from progressing to necrosis is to identify and treat the ischemia as early as possible. Early (<2 days) combination treatment with hyaluronidase is associated with the full resolution of the complication. CLINICAL QUESTION/LEVEL OF EVIDENCE:Therapeutic, IV. 10.1097/PRS.0000000000001579
    Risk Comparison of Filler Embolism Between Polymethyl Methacrylate (PMMA) and Hyaluronic Acid (HA). Nie Fangfei,Xie Hongbin,Wang Guanhuier,An Yang Aesthetic plastic surgery BACKGROUND:The incidence of vascular complications varies among different fillers. The main purpose of this study was to compare the risk of embolism between PMMA (Artecoll) and hyaluronic acid (HA, Restylane) after artery injection. METHODS:Rabbit ears were injected via the central artery with 0.1 ml PMMA (group A), 0.1 ml HA (group B), 0.2 ml PMMA (group C), or 0.2 mL HA (group D), respectively. The formation of transparent emboli was monitored right after injection. Tissue necrosis and histopathological changes were analyzed on day 7. RESULTS:With 0.1 ml injected volume, PMMA was dispersed within a few minutes and only 5% of the injected ears had mild necrosis on day 7, while HA tended to form obvious transparent emboli, an indication of blood vessel clotting, and 60% of injected ears showed necrosis on day 7. With 0.2 ml injected volume, PMMA had a risk of complete blood vessel clotting in between 0.1 ml PMMA group and 0.1 ml HA group, and 30% of injected ears had necrosis; in contrast, 100% of 0.2 ml HA-injected ears showed transparent emboli and necrosis. The necrosis areas were significantly increased in the HA groups compared with PMMA groups at the same injection volumes. HA injection also caused dilation of small blood vessels. CONCLUSION:At the same injection volume, PMMA had less risk of embolism compared with HA. With increased injection volume, there were increased risks of embolism and necrosis for both PMMA and HA. NO LEVEL ASSIGNED:This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 . 10.1007/s00266-019-01320-w
    Livedo reticularis and skin necrosis due to hyaluronic acid embolism. Borregón-Nofuentes Paloma,Avilés-Izquierdo José Antonio,Martínez-Izquierdo M Ángeles,Ribé-Bernal Lucas,Pulido-Pérez Ana,Moya-González M Dolores,Lázaro-Ochaita Pablo JAMA dermatology 10.1001/jamadermatol.2013.1361
    The Role of Hyaluronidase for the Skin Necrosis Caused by Hyaluronic Acid Injection-Induced Embolism: A Rabbit Auricular Model Study. Li Jiqing,Xu Yinglin,Wang Yu,Hsu Yuchun,Wang Peng,Li Jihua Aesthetic plastic surgery BACKGROUND:Skin necrosis is considered the most serious complication of hyaluronic acid dermal filler injection procedures. To effectively treat skin necrosis, hyaluronidase injection is one of the essential preventative treatments, and yet optimal complication management remains an unmet need. Therefore, this paper investigates the effects of hyaluronidase injection timing on the treatment of skin necrosis. METHODS:In an in vitro experiment, the carbazole method was used to determine the degradation time of hyaluronic acid gels in a large volume of hyaluronidase. In vivo experimental rabbit ear models were developed to simulate the skin necrosis caused by hyaluronic acid and the test animals distributed into five groups. Except one control group, the other four groups were injected with a large volume of hyaluronidase as treatment at 2 h, 4 h, 8 h and 16 h, respectively, after models were built. The necrosis degree of models was analyzed with necrotic area and histologic examination on the postoperative 7th day. Besides, temperatures of rabbit ears were observed to demonstrate the healing process of flap models. RESULTS:The average necrotic area of flaps in the 2-h and 4-h injection groups showed a significant difference compared with that of the control group (p < 0.05; p < 0.05). The histologic examination showed that there were HA embolisms, vascular thrombolytic recanalization and arteriovenous thromboses in the survival area. In addition, the mean temperatures of the rabbit ear flaps fluctuated over time and showed clear differences between distal and proximal parts. CONCLUSIONS:The area of flap necrosis positively correlates with injection timing of the large volume of hyaluronidase. More importantly, when injection timing is within 4 h, treatment effectiveness will be significantly improved. NO LEVEL ASSIGNED:This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 . 10.1007/s00266-019-01398-2
    Intravenous Hyaluronidase with Urokinase as Treatment for Arterial Hyaluronic Acid Embolism. Foissac Rémi,Kestemont Philippe,Camuzard Olivier Plastic and reconstructive surgery 10.1097/PRS.0000000000002448
    Local Cooling as a Step of Treatment for Tissue Ischemia Caused by Hyaluronic Acid Injection-induced Embolism-A Report of 9 Cases. Zhang Chen,Ge Chunying,Du Chunxiao,Li Jieqi Plastic and reconstructive surgery. Global open Hyaluronic acid injection is 1 of the most popular procedures in facial rejuvenation and augmentation. It is widely popular in the cosmetic surgery due to several advantages, which include rapid effect, minimal injury, and a short postoperative recovery period. With continuous increase in hyaluronic acid injections, many cases of hyaluronic acid injection-induced embolism have been reported. At present, methods for early treatment of hyaluronic acid injection-induced embolism include local injection of hyaluronidase, topical application of nitroglycerin ointment, massage, hot compression, and intravenous injections of antibiotics and hormones. Although early warm massage may facilitate hyaluronic acid degradation by hyaluronidase, local application of heat will also increase metabolic rate in the tissue, thereby reducing the ischemic tolerance of the tissue. Therefore, in this study, warm massage was limited to the first 30 minutes after hyaluronidase injection and was followed by local cooling using a gauze pad soaked with antibiotic saline solution. Excellent therapeutic effects were achieved with this approach. The methods of treatment for tissue ischemia caused by hyaluronic acid injection-induced embolism and clinical cases are introduced in the article. 10.1097/GOX.0000000000001824
    Comparison of Intra-arterial and Subcutaneous Testicular Hyaluronidase Injection Treatments and the Vascular Complications of Hyaluronic Acid Filler. Wang Muyao,Li Wei,Zhang Yan,Tian Weidong,Wang Hang Dermatologic surgery : official publication for American Society for Dermatologic Surgery [et al.] BACKGROUND:Hyaluronidase is a key preventative treatment against vascular complications of hyaluronic acid (HA) filler injection, but the degradation profile of HA to hyaluronidase is limited, and the comparison between intra-arterial and subcutaneous injections of hyaluronidase has not been studied. OBJECTIVE:To evaluate HA degradation to hyaluronidase and compare different treatments between intra-arterial and subcutaneous testicular hyaluronidase injections. MATERIALS AND METHODS:The authors observed HA degradation to hyaluronidase in vitro via microscopic examination and particle analysis. Rabbit ears were used for the in vivo study. There were 2 control groups receiving ligation or HA-induced embolism in the arteries, respectively, and 2 intervention groups receiving hyaluronidase treatments in different regions. The laser Doppler blood perfusion monitoring measurements were made at defined time points, and biopsies were taken on Day 2. RESULTS:Nearly, all of the HAs degraded in vitro at the 1-hour time point. Subcutaneous hyaluronidase treatment showed better recovery of blood perfusion. Histology showed severe inflammation in the embolism group and mild inflammation in the intervention groups. CONCLUSION:A complete enzymatic degradation of HA filler to hyaluronidase needs a certain time, and subcutaneous hyaluronidase treatment may be the better option. 10.1097/DSS.0000000000000955
    An Islanded Rabbit Auricular Skin Flap Model of Hyaluronic Acid Injection-Induced Embolism. Zhuang Yan,Yang Mingyong,Liu Chunjun Aesthetic plastic surgery BACKGROUND:Hyaluronic acid (HA) injection-induced embolism is a rare but severe complication. This article is aimed to introduce an islanded rabbit auricular skin flap model of HA injection-induced embolism and to study its pathophysiological progress. METHODS:An islanded skin flap was elevated based on the proximal central auricular artery/vein. Eighteen rabbits were randomized into three groups. Ten, twenty, and forty microliters of HA were injected into the central auricular artery in each group, respectively. Flap fluorescence angiography was performed. One-way ANOVA was used to compare fluorescence area at different time points and between dose groups. Two rabbits in each group were randomly chosen for histology examination. In addition to regular HE staining, Alcian Blue staining was performed to better show the existence of HA in the vessel lumen. RESULTS:The mean calculated fluorescence area was 64.41 % on POD 1, 79.77 % on POD 3, 88.20 % on POD 5, and 92.03 % on POD 7 in 10 μl group; 60.51 % on POD 1, 58.84 % on POD 3, 71.20 % on POD 5, and 76.54 % on POD 7 in 20 μl group; 21.60 % on POD 1, 3.08 % on POD 3, 2.91 % on POD 5, and 7.52 % on POD 7 in 40 μl group. In all three groups, infiltration of eosinophilic granulocytes was observed in the muscular layer of both artery and vein. CONCLUSION:Our study successfully created a rabbit auricular skin necrosis model of HA embolism, which provided a valuable animal model for further investigation of the pathophysiological progress and the efficacy of potential treatments. NO LEVEL ASSIGNED:This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 . 10.1007/s00266-016-0630-0
    Intravenous Hyaluronidase with Urokinase as Treatment for Rabbit Retinal Artery Hyaluronic Acid Embolism. Chiang ChengAn,Zhou ShuangBai,Chen ChuHsin,Ho Dave S,Zhang HuiZhong,Liu Kai Plastic and reconstructive surgery BACKGROUND:Although various salvage methods have been proposed to treat intraretinal artery hyaluronic acid embolism, their applications are still limited by various factors. The authors investigated the effectiveness of intravenous hyaluronidase with urokinase for resolving retinal artery hyaluronic acid embolism. METHODS:The anatomy of rabbit ophthalmic and fundus arteries (retinal and choroid artery) was studied. Approximately 0.35 ml of hyaluronic acid was injected into the ophthalmic artery to create a retinal artery embolism model. The rabbits were grouped randomly (groups A, B, C, D, E, and F) and given hyaluronidase with urokinase intravenously at different postobstruction time points (10, 20, 30, 40, 50, and 60 minutes). Saline was given to the control group. Fundus vascular (retinal and choroid artery) reperfusion status and the effectiveness of the solution on the obstruction of each group were observed for 5 days. RESULTS:The animal model closely imitated actual hyaluronic acid ophthalmic/retinal artery obstructions. Three vascular conditions were observed after hyaluronidase with urokinase injection: total, partial, and no reperfusion. Groups A, B, and C showed a significantly higher overall solution effectiveness rate (total/partial reperfusion) compared with the control group (p = 0.001, p = 0.001, and p = 0.005, respectively). Solution effectiveness in groups D, E, and F showed no difference compared with the control group (p = 0.628, p = 1.000, and p = 1.000, respectively). The effectiveness of the solution drops dramatically if given after 30 minutes of obstruction. CONCLUSIONS:The authors' method can indeed help resolve retinal artery hyaluronic acid obstruction. Intravenous hyaluronidase with urokinase technique shows possible potential to become a standardized treatment protocol for intraretinal artery hyaluronic acid embolism with further clinical tests. 10.1097/PRS.0000000000002803
    Experimentally Induced Arterial Embolism by Hyaluronic Acid Injection: Clinicopathologic Observations and Treatment. Chen Yin,Zhang You-Liang,Luo Sheng-Kang Plastic and reconstructive surgery BACKGROUND:Although major complications of hyaluronic acid injection rarely occur, with the rapidly growing number of procedures performed and their expanding applications, such complications warrant greater attention. Our study was designed to explore optimal treatment methods for hyaluronic acid-related vascular occlusion. METHODS:In the first part of the study, 60 rats were given intraarterial hyaluronic acid injected into the bilateral inferior epigastric arteries to establish an animal model, and were euthanized at different postinjection time points. The inferior epigastric artery was retrieved for pathologic examination. In the second part of the study, bilateral abdominal flaps supplied by the inferior epigastric artery were elevated in six groups of rats, and hyaluronic acid was injected into the right side, with each group receiving a different intervention. The flap survival rate was calculated and analyzed. RESULTS:In the first part of the study, pathologic examination revealed that the composition of the emboli caused by arterial hyaluronic acid-induced occlusion changed from pure hyaluronic acid to a hyaluronic acid-thrombus mixture. In the second part of the study, flap survival rates (mean percentages) were as follows: group A, 43.29 ± 9.28 percent; group B, 54.17 ± 10.86 percent; group C, 59.27 ± 13.40 percent; group D, 64.37 ± 8.61 percent; group E, 71.92 ± 19.06 percent; and group F, 57.47 ± 13.64 percent. Group A differed significantly from groups B, C, D, and E (p < 0.001). No significant difference was observed between groups A and F (p > 0.05). CONCLUSIONS:The combined use of intravenous or subcutaneous hyaluronidase and urokinase was most effective in treating hyaluronic acid injection-related arterial embolism after 45 minutes and 24 hours. This treatment may be ineffective after 48 hours. 10.1097/PRS.0000000000005456